tbuckley/cabot-search huggingface dataset:
Abstract 12848: Infections Requiring Hospitalization in Patients One Year Post Heart Transplant
Authors: Max Jason, Rodolfo Alpizar-Rivas, Rohith Palli, Jeffrey Alexis, Anna Sorensen, Christine Hay
Journal: Circulation (2022)

Introduction: Immunosuppression of heart transplant (txp) recipients increases risk of infection. This study will identify the most common pathogens and characterize the most at-risk patients. Methods: We performed a single center retrospective cohort study at the University of Rochester. Demographics, pretransplant characteristics, and infections requiring rehospitalization were obtained (table 1) from electronic records of patients who received a txp from January 1, 2011 through July 1, 2020. Chi-square, t-test, and Wilcoxon rank-sum test assessed association between mortality, infection risk and other variables. Results: We identified 132 patients who received txp but excluded 4 due to incomplete data, 10 (7.6%) patients died during index admission while 12 (9.4%) more patients died in the year following their txp. Infections occurring 1 month post txp were associated with mortality (p-adj 0.026). Prior sternotomies (n=65, 50.8%) were associated with both mortality and bacterial infection (p-adj &lt;0.01). EBV mismatch (n= 7, 5.5%) was associated with infections during months 7-12 post-txp (p-adj 0.027). Unknown pathogens (20) were the most common cause of rehospitalization followed by Pseudomonas (13) (Fig 1). Conclusions: Our study identifies patient risk of rehospitalization due to infection in the year following txp. Prior sternotomies were associated with worse outcomes. We hypothesize this is due to scarring and is worth studying prospectively. Patients with EBV mismatch had higher rates of infections in months 7-12, a finding not previously described. There was higher mortality associated with infections that required hospitalization in the first month.
Abstract 12777: The Lingering Snag in Era of Mechanical Pumps: A Case of Acute Pump Thrombosis Immediately After Heartmate 3 Implantation
Authors: Anureet Malhotra, Amandeep Goyal, Tarun Dalia, Hassan Farhoud, Poonam Bhyan, Andrija Vidic, Bhanu Gupta, Zubair Shah, Travis Abicht
Journal: Circulation (2022)

Background: Pump thrombosis (PT) remains a dreaded complication of left ventricle assist device (LVAD) implantation. PT immediately after HeartMate 3 (HM3) implantation is rare but should be kelp in mind if early low flow alarms are noted. Case: A 57-year-old male with ischemic cardiomyopathy, Stage D heart failure (LVEF ~20%), INTERMACS category 3 on 5mcg/kg/min Dobutamine drip underwent advanced heart failure therapy evaluation and was deemed suitable candidate for LVAD implant. His ECHO showed LVIDD 6.04 cm and LV Diastolic Volume Index 122 mL. He underwent HM3 implantation via left anterior thoracotomy and upper-hemi sternotomy on 5/24/2022. Surgery was successful and the patient was taken off bypass. Pre-implant some LV trabeculations and debris were removed. However, less than 1 hour from being off bypass, the low flow alarms began which did not resolve after volume and blood pressure optimization. No RV failure was noted on TEE. Decision was made to re-open the sternum. Upon exploration, no compression of the outflow graft was noted, and inlet cannula was not mispositioned. Inspection of LVAD inlet and outlet cannula showed significant amount of white thrombus (Figure 1) and device was ultimately exchanged. Thrombus was confirmed on histopathological analysis. Post-operatively no low flow alarms were noted after pump exchange. Factor V Leiden screen and protein C activity were normal and Antithrombin 3 was falsely low (due to recent thrombus) on post-op day 1. Discussion: This is the second case of HM 3 device thrombosis within 1 hour of implant in the literature. Most of the earlier reported cases were on post-Op Day 3. The etiology of PT is unknown and further investigation is required to elucidate the same. This case will create awareness among physicians to keep PT in differentials when low flow alarms are encountered immediately post-op despite volume and BP optimization.
Abstract 12766: Tropsensor: A Rapid Non-Invasive Transdermal Solution For Troponin Measurement
Authors: Jitto Titus, Alan H Wu, Siddharth Biswal, Atandra Burman, Allan S Jaffe
Journal: Circulation (2022)

Introduction: Early identification of Acute Myocardial Injury can prompt rapid triage and appropriate interventions to improve clinical outcomes. Over 10 million patients present at the ED with chest-pain, with the majority due to non-cardiac causes, resulting in unnecessary burdens for Emergency Departments (ED). An instant non-invasive method to measure cardiac troponin (cTn) would therefore be of great benefit. Identified need: All Guidelines recommend the use of high sensitivity (HS) cTn for the diagnosis of acute coronary syndromes (ACS). Current biochemical biomarker testing relies on labeling the cTn with turnaround times often an hour or more. Point-of-care solutions reduce the test time, but still depend on the proper handling of samples and blood processing techniques that could lead to difficulties. Tropsensor provides a non-invasive alternative to standard of care (SOC) hs-cTn measurements without the need for a blood draw. The molecular infrared spectroscopy-based transdermal device provides a cTn readout within 5 minutes and allows for serial measurements without any of the delays or complications of blood draws. Methods: A 26-patient (consented and IRB approved) study was conducted at Zuckerberg San Francisco General Hospital with recruitment based on ACS-related presenting symptoms at the ED. Wrist-worn Tropsensor was used on the patients while the corresponding troponin was determined using a high sensitivity (SOC) assay (Siemens ADVIA Centaur) via a blood draw. Results and conclusions: A Pearson’s correlation of 82% with the hs-cTnI was observed. AMI diagnosis sensitivity was 100%, Specificity=50%, PPV=81.8%, NPV=100% and accuracy=84.6%. The Tropsensor modality seems to provide data similar to that of a hs-cTn assay. If so, it would accelerate the assessment of patients presenting with chest pain. By not requiring a blood draw, the Tropsensor could provide a rapid, safe, standardized and reliable source for cTn while allowing bedside serial trending. It thus has the potential to streamline cardiac care workflow by ruling-out many non-cardiac patients and identifying those with high values who are at risk. Such an approach has the potential to facilitate appropriate patient triage towards early discharge of emergent treatment.
Abstract 13824: Lifestyle Management for Cardiac Health With Deep Learning of Biomechanical Dynamics
Authors: Kiirthanaa Gangadharan, Qingxue Zhang
Journal: Circulation (2022)

Physical activities are of great values and, with appropriate principles, are reported to be clinically effective for rehabilitation from cardiac diseases. The physical activity-based lifestyle stimulation is thus highly promising to foster cardiac health management. Target the challenge that, the understanding of how different body locations contribute to the physical activity detection accuracy is still limited, we propose to leverage deep learning to investigate comprehensively seven body locations and six signal channels for each location. They are the chest, forearm, head, shin, thigh, upper-arm, and waist locations, and for each location, there are tri-axis acceleration signals and tri-axis gyroscope signals. In total there are forty-two combinations. The proposed convolutional neural network, when applied on each of the forty-two cases, yields a comprehensive comparison of these configurations in terms of physical activity type detection accuracy. Evaluated on fifteen subjects and six different physical activities, including climbing downstairs, climbing upstairs, jumping, lying, running/jogging, and walking, the determined optimal configuration is the chest location and the accelerometer axis-Y channel, with an accuracy of 95.1%. This study has not only maximized the physical activity detection accuracy through optimal configuration determination, but also deepened our understanding of how biomechanical dynamics are generated through different body locations and sensor channels. The research findings will greatly benefit cardiac health management.
Abstract 13829: Low Density Lipoprotein Receptor on the Immune Cells Influence the Atherosclerosis Progression in C57bl/6 Mice
Authors: Jitendra S Kanshana, Martha Bustos, APOORVA NARAIN, Joshua Nguyen, Kruthika Doreswamy, Alison B Kohan
Journal: Circulation (2022)

Introduction: Atherosclerosis is the leading cause of cardiovascular diseases (CVDs). Over the past three decades, the clinical focus has been reducing plasma lipids and other traditional risk factors to reduce cardiovascular mortality. More recently, the CANTOS trial showed that inflammation is a significant additional risk factor for CVDs. Regulatory T cells (Tregs) are well known to protect the aorta from the inflammatory burden, but clinically how to induce these cells is not known. Hypothesis: LDLr is expressed on various immune cells, including Tregs. Recently, our lab found that modulating the lipid metabolism through LDLr in Tregs protects mice from colitis. Collectively, our data illustrate that LDLr plays an essential role in T cell homeostasis and function that may impact atherosclerosis progression. Therefore, our goal in this study is to test whether the absence of LDLr in immune cells alters the development of atherosclerosis. Methods: We used C57BL/6J male mice, which were lethally irradiated and transplanted with either LDLr-/- or WT bone marrow (BMT). To induce atherosclerosis, we blocked hepatic triglyceride clearance (antisense oligonucleotides) and fed mice with a high-fat diet for 12 weeks. We then collected blood and aorta to assess the extent of atherosclerosis. Results: Mice transplanted with LDLr-/- bone marrow have a lower percentage of T lymphocytes such as Th1 cells, Th1/Th2 hybrid cells, and pro-inflammatory M1 macrophages in the aorta compared to WT BMT aorta. Conversely, LDLr-/- BMT mice had a lower percentage of total Tregs but a significantly higher percentage of Tregs expressing the anti-inflammatory cytokine IL-10 and a lower percentage of Tregs co-expressing the pro-inflammatory marker T-bet compared to WT BMT aorta. Also, LDLr-/- BMT mice exhibited a 2-fold increase in plasma IL-10 compared to WT BMT plasma. Conclusion: Altogether, the current study's finding suggests that the loss of the LDLr in the immune compartment (bone marrow) can induce a significant change in the aortic immune cells and may be a future target for augmenting the protective Tregs population in CVD patients.
Abstract 14145: Relationship of Pharmacokinetic and Biomechanical Parameters With Intraplaque Haemorrhage- An <i>in vivo</i> Carotid MR Imaging Study
Authors: Umar Sadat, Ammara Usman
Journal: Circulation (2022)

Introduction: Atheromatous neovessels with high permeability have been implicated in the evolution of intraplaque haemorrhage (IPH). In vivo quantification of vasa vasorum permeability is possible using dynamic-contrast enhanced-magnetic resonance (DCE-MR) imaging. Hypothesis: In vivo relationship of extent of leakiness of neovessels with critical biomechanical forces i.e. stress and strain in atheroma and with IPH remains unreported. Methods: Patients with mild to severe carotid artery stenosis underwent DCE-MR imaging of their bilateral carotid arteries on a 3 Tesla MR system, using TRICKS method. A two-compartment Patlak model was used to generate a parametric map showing partial plasma volume (vp) and K trans. FEA simulations were performed for stress and strain analyses. For histological analysis, carotid plaques were processed and stained. Results: Sixteen patients underwent carotid MR imaging. The two groups were comparable for their demographics and co-morbidities. Peak structural stress (PSS) and peak strain (P1) were significantly higher in symptomatic versus asymptomatic patients (p=0.002 and 0.009 respectively). Carotid atheroma with IPH had higher PSS and P I compared to those without IPH [p=0.036 and 0.009]. Variations in stress during one cardiac cycle was significantly greater among plaques with IPH (p=0.01); variation in strain was greater in atheroma with IPH [p=0.04]. Adventitial K trans was higher in carotid atheroma of symptomatic patients than asymptomatic cohort (p= 0.016). Plaque K trans , adventitial and plaque v p were however comparable for both patient cohorts (p= 0.81, 0.96, 0.36 respectively). Adventitial K trans and plaque v p were higher in atheroma with IPH (p= 0.04, 0.01) but comparable for plaque K trans and adventitial v p (p=0.46, 0.88 respectively). A strong correlation was observed between variations in strain during the cardiac cycle with adventitial K trans for plaques with IPH [Pearson r : 0.84, p=0.03]. Conclusions: A strong correlation exists between adventitial neovessel permeability and variations in strain in atheroma with IPH. Carotid atheroma with IPH have higher biomechanical stresses and strain and variations in these critical biomechanical conditions compared to non-IPH atheroma.
Abstract 13223: Calcium/Calmodulin-Dependent Protein Kinase II Decreases KCNH2-Related Current During Sustained Adrenergic Receptor Stimulation
Authors: Enoch Amarh, Abdullah A Assiri, Firoj K Sahoo, Andy Hudmon, James E Tisdale, Todd C Skaar, Brian R Overholser
Journal: Circulation (2022)

Introduction: KCNH2 codes for a potassium channel that mediates the primary cardiac repolarizing current, I Kr . Calcium/calmodulin-dependent protein kinase II (CaMKII) modulates several ion channels, is enhanced during sustained β-adrenergic receptor (βAR) stimulation, and is proarrhythmic. Furthermore, states of enhanced βAR stimulation/CaMKII activity, such as heart failure, alter microRNA (miR) expression profiles that suppress protein expression. Hypothesis: CaMKII decreases KCNH2-related current during sustained βAR stimulation through miR regulation. Methods: Putative miR binding sites (n=327) on KCNH2 3′-UTR were identified with bioinformatic tools. Binding sites were then constructed into a pIS0 plasmid, amplified, and transfected into hiPSC-cardiomyocytes. Cells were subjected to sustained βAR stimulation (Isoproterenol: 100 nM, 1 μM), constitutively active δCaMKII (Thr287Asp), or control conditions. Next-generation sequencing was used to identify altered miR binding sites expression and endogenous miR alterations. Whole-cell, voltage-clamp experiments were performed in HEK293 cells expressing KCNH2 and δCaMKII T287D . Cells were treated with isoproterenol, and miR mimics were used for validation of the bioassay. Results: Nine and eight predicted miR binding sites were downregulated in the CaMKII group (Δlog fold: -0.287 to -0.59, p&lt;0.05) and sustained βAR group (Δlog fold: -0.29 to -0.72, p&lt;0.05), respectively. Thirty miRs were predicted to bind to these sites on KCNH2 3′-UTR, of which seven were selected for validation based on a Δlog fold &lt; -0.6 in one group (n=4) or &lt; -0.5 in both treatment groups (n=3). Mimics of all seven miRs reduced KCNH2 protein expression, and three decreased KCNH2 currents compared to control (p&lt;0.05). Sustained βAR stimulation decreased peak activation current in cells expressing both KCNH2 and δCaMKII T287D by 25% (17±7 pA/pF, p = 0.03) and tail current density by 27% (21±9 pA/pF, p = 0.03), but had no effect on currents in cells expressing only KCNH2. Conclusions: CaMKII hyperactivity alters miR expression profiles and decreases KCNH2 function during sustained βAR activation. The effect of the identified miRs on arrhythmia susceptibility with enhanced CaMKII activity warrants further study.
Abstract 14317: The Prevalence of Motile Ciliary Gene Variants in Children With Transposition of the Great Arteries and Tetralogy of Fallot
Authors: Alison J Howell, Andrea Pisesky, Wallace Wee, Kyle Runeckles, Roderick Yao, Jade Bouwmeester, Sandar Min, Seema Mital, Sharon Dell, Lynne E Nield
Journal: Circulation (2022)

Introduction: Motile ciliary dysfunction plays a central role in the pathogenesis of respiratory abnormalities and congenital heart disease (CHD). The role of ciliary gene variants in the non-heterotaxic CHD population is not well characterised. Methods: This single-centre retrospective cohort study aimed to determine the prevalence of Primary Ciliary Dyskinesia (PCD) gene variants in children with isolated Transposition of the Great Arteries (TGA) and Tetralogy of Fallot (TOF). Patients with whole genome sequencing between 2008-2018 were included. We identified pathogenic (P) or likely pathogenic (LP) single-nucleotide variants (SNVs) and short insertion/deletions (indels) in coding regions of 45 genes known to cause PCD. Patient characteristics and associated respiratory outcomes were evaluated from chart reviews. Results: PCD gene variants were found in 2.9% (5/172) TGA and 3.8% (10/264) TOF patients. Thirteen probands were heterozygous for P/LP SNVs/ indels; CCDC40 N=6, DNAH11 N=2, SPAG1 N=2 and one each of DNAH8/DNAAF1/ARMC4. Two were compound heterozygotes for variants in DNAH11 and DNAH8. At last follow-up, mean age was 14.5 years (SD 6.8, 57.9% male) and 7 deaths had occurred. Asthma was diagnosed in 10.5% TGAs and 8.1% TOFs with 3.9% and 7.3% respectively requiring hospitalisation for primary respiratory illness. In the variant positive subgroup, 5/15 had respiratory abnormalities - bronchiectasis (N = 1), asthma (N = 2), neonatal cough (N = 1), ventilator-associated pneumonia (N = 2). Additional cardiac anomalies occurred in 53% (8/15) - abnormal systemic veins (N = 3), situs inversus, dextrocardia (N = 1), right arch (N = 5), hypoplastic right ventricle (N = 1). An abnormal coronary pattern was seen in 4/5 TGAs. Vaginal and renal agenesis each occurred in 1 patient. Conclusions: Our findings suggest a high prevalence and potential association of ciliary gene variants with respiratory outcomes and situs anomalies in non-heterotaxy CHD.
Abstract 14230: Comparing Stress Echocardiography Parameters of Transgender Women With Their Cisgender Counterparts: The Mayo Clinic Women’s Heart Clinic
Authors: Connor D Walsh, Fadi Adel, John Bretzman, Philip Sang, Patricia A Pellikka, Rekha Mankad
Journal: Circulation (2022)

Introduction: Stress echocardiography (SE) is a common functional imaging modality used for the detection of symptomatic coronary artery disease (CAD). Currently, the interpretation of SE relies on sex-based comparators for reporting parameters, including exercise time and functional aerobic capacity. These parameters are based on the cisgender male and female populations but have not been studied among transgender (TG) patients. Thus, we sought to characterize the SE parameters among a group of TG women. Methods: We designed a case-control study of TG women who underwent a SE at the Mayo Clinic. Each TG patient was age-matched with 2 cis-males and 2 cis-females. Demographics, medical history, and SE data were extracted. Conditional logistic regression analysis was performed to compare the TG cohort with each cisgender cohort separately. Results: Among the 43 TG females (age 57.7±9 years, 94.9% white), the prevalence of CAD was less than in cis-males (p=0.013) but similar to cis-females. For SE parameters, TG females had higher resting heart rates than cis-males (median [Q1, Q3]: 80 [71,93] vs 70 [64, 77]; p=0.002). Double product (24816 [21156, 27864] vs 26864 [22444, 30660]; p=0.016), exercise time (7.3 minutes [6,9] vs 8.5 [7.2, 9.5]; p=0.041), and metabolic equivalents (8.2 [7, 10] vs 9.5 [8.2, 10.5]; p=0.018), were all lower in TG females than cis-males. Exercise ejection fraction was higher in the transgender cohort than in cis-females (70 [70, 75] vs 70 [65, 70]; p=0.007). There was no difference in functional aerobic capacity or in the rest or stress wall motion score indices among the groups. Finally, there was no difference in the prevalence of positive electrocardiogram or SE studies. Conclusion: In conclusion, we report for the first time SE profiles for TG females which display an overall distinct phenotype compared to cis-males and cis-females. Larger prospective studies are warranted to further define these parameters for the TG population.
Abstract 14185: Higher Rates of Heart Failure Hospitalizations for V142I ATTR-CM Patients With Atrial Arrhythmias and Conduction Disease
Authors: Austin Rim, Rebecca Steinberg, Sreeram Yalamanchili, Rahul Patel, Dhanish Revanth Rangaswamy Nandakumar, Matthew T Brown, Kunal Bhatt
Journal: Circulation (2022)

Introduction: TTR cardiac amyloidosis (ATTR-CM) is a progressive, infiltrative cardiomyopathy that is characterized by the deposition of amyloid fibril extracellularly in the myocardium. Patients with ATTR-CM are known to be at higher risk for arrhythmias and conduction disease, likely due to changes in the cardiac anatomy and disruption of the conduction system by amyloid fibrils. Our study aims to determine whether presence of an arrhythmia or conduction disease is associated with mortality and heart failure hospitalizations in patients with ATTR-CM and V142I mutation. Hypothesis: Patients with arrhythmia or conduction disease will have higher rates of heart failure hospitalizations (HFH) and mortality than those without it. Methods: We conducted a retrospective chart review of patients diagnosed with ATTR-CM with V142I mutations enrolled in Emory University's Cardiac Amyloidosis Clinic between January 2014 and April 2022. Kaplan-Meier (KM) curves stratified by presence of atrial arrhythmia, ventricular arrhythmia, or conduction disease were generated for mortality and first HFH within 2 years of initial diagnosis. Log-rank test was used to compare KM curves. A p-value &lt; 0.05 was considered significant. Results: 111 patients were identified to have ATTR-CM with V142I mutation. 51.4% (57) of the patients had an atrial arrhythmia (fibrillation or flutter), 46.8% (52) had conduction abnormalities (defined as second or third degree heart block). 44.1% (49) had ventricular arrhythmias (including NSVT, sustained VT, and/or VF). Patients who had atrial arrhythmia and conduction disease were more likely to have HFH within 2 years compared to those who did not (p = 0.0011, p = 0.044 respectively). Patients with atrial arrhythmia, ventricular arrhythmia, or conduction disease were not at higher risk of mortality within 2 years (p=0.21, p=0.71, p=0.66 respectively). Conclusions: For patients with ATTR-CM with V142I mutation, atrial arrhythmia and conduction disease were risk factors for HFH within 2 years. Atrial and ventricular arrhythmia and conduction disease were not associated with higher mortality within 2 years.